MicroRNA-141 and its associated gene FUS modulate proliferation, migration and cisplatin chemosensitivity in neuroblastoma cell lines

Oncol Rep. 2016 May;35(5):2943-51. doi: 10.3892/or.2016.4640. Epub 2016 Feb 26.

Abstract

In the present study, a novel signaling pathway of microRNA-141 (miR-141)/fused in sarcoma (FUS) was investigated in neuroblastoma (NB). Gene expression of miR-141 was evaluated in 6 NB cell lines. IMR-32 and SH-SY5Y cells were transduced with the miR-141 mimic lentivirus. The effects of miR-141 upregulation on cell proliferation, cell division, migration, chemosensitivity and in vivo explants were evaluated by MTT, cell cycle, wound-healing, cisplatin sensitivity and in vivo tumor growth assays, respectively. The correlation between miR-141 and the FUS gene was evaluated by luciferase assay and qRT-PCR. FUS was also downregulated in IMR-32 and SH-SY5Y cells to evaluate its impact on NB regulation. miR-141 was downregulated in both MYCN‑ and non-MYCN‑amplified NB cell lines. In the IMR-32 and SH-SY5Y cells, lentivirus-induced miR-141 upregulation inhibited cancer proliferation, cell cycle progression, migration and increased cisplatin chemosensitivity in vitro. In addition, miR-141 upregulation reduced the in vivo growth of IMR-32 tumor explants. FUS was found to be inversely regulated by miR-141 in NB. Small interfering RNA (siRNA)-induced FUS downregulation had similar tumor-suppressive effects as miR-141 upregulation on NB cell proliferation, cell cycle progression, migration and cisplatin chemosensitivity. Our data indicate that miR-141 and the FUS gene, which are inversely correlated, play significant functional roles in regulating human NB.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm
  • Female
  • Gene Expression
  • Humans
  • Mice, Nude
  • MicroRNAs / physiology*
  • Neoplasm Transplantation
  • Neuroblastoma / genetics
  • Neuroblastoma / metabolism*
  • Neuroblastoma / pathology
  • RNA-Binding Protein FUS / genetics*
  • RNA-Binding Protein FUS / metabolism
  • Tumor Burden

Substances

  • Antineoplastic Agents
  • FUS protein, human
  • MIRN141 microRNA, human
  • MicroRNAs
  • RNA-Binding Protein FUS
  • Cisplatin